A transition-prone brain state precedes spontaneous behavioral switching

Abstract Animals exhibit behavior in the absence of external stimuli or explicit tasks. Is the initiation of such spontaneous behavior shaped by internal brain states in a predictable manner? If so, does it engage specific brain circuits independent of behavioral form? Here, we studied the initiation of uninstructed behaviors of head-fixed mice in two contexts: a virtual burrow and a running wheel. Across both contexts, mice spent most of the time in quiet wakefulness and spontaneously initiated bouts of egress (exiting the burrow), running, or grooming. We employed functional ultrasound imaging (fUS) to record whole-brain activity and to identify whether the initiation of spontaneous behavior could be predicted from hemodynamic signals. We first identified distinct hemodynamic patterns associated with each behavior and subsequently performed time-resolved decoding to predict behavioral transitions from fUS data. We found that whole-brain hemodynamic signals could decode spontaneous egress and running around 10 seconds before their onset, a timescale that cannot be accounted for by preceding behavioral changes alone. Furthermore, we found a network of regions, including the medial septum (MS), that decreased their signal several seconds before the onset of egress and running. Mimicking this decrease by inhibiting neurons in the MS via optogenetics increased the probability of egress, running, and grooming. Through this unbiased approach, our work sheds light on a whole-brain transition-prone state that precedes uninstructed behavior transitions. Competing Interest Statement The authors have declared no competing interest.